Chiral oxime ethers in asymmetric synthesis. O-(1-Phenylbutyl)benzyloxyacetaldoxime, a versatile reagent for the asymmetric synthesis of protected 1,2-aminoalcohols, α-amino acid derivatives, and 2-hydroxymethyl nitrogen heterocycles including iminosugars

Abstract

Addition of a range of organolithium and Grignard reagents to (E)-O-(1-phenylbutyl)benzyloxyacetaldoxime 1 in the presence of boron trifluoride diethyl etherate is highly diastereoselective. The resulting hydroxylamines undergo N-O bond cleavage upon treatment with zinc-acetic acid or molybdenum hexacarbonyl to give, after N-protection, protected 1,2-aminoalcohols 3 in high enantiomeric purity. Debenzylation of 3a and 3d gave N-Boc (R)-alaninol and (S)-phenylalaninol respectively. The hydroxylamines 2 also serve as alpha-amino acid precursors, 2i being converted into N-formyl-(R)-alaninyl-(S)-(4-bromo)phenylalanine ester 7, the N-terminal dipeptide of a natural depsipeptide. The versatility of the 1,2-aminoalcohol derivatives was further illustrated by their conversion into 5-, 6- and 7-membered 2-hydroxymethyl nitrogen heterocycles 15-19 in high enantiomeric excess by a ring-closing metathesis reaction. Further reaction of the dihydropyrrole 15 gave the iminosugar 1,4-dideoxy-1,4-imino-D-ribitol.

Transition metals in organic synthesis: Highlights for the year 2005

“…A large variety of ring systems were prepared via alkene-alkene RCM using ruthenium catalysts [441] including, furans and pyrroles [1062], macrocycles [1063][1064][1065][1066][1067][1068][1069][1070][1071], five-to nine-membered unsaturated cyclic amines [498,519,898,[1072][1073][1074][1075][1076][1077], cyclooctenes [1078], chiral azepin-3-ols and azocin-3-ols [1079], oxepinand oxocin-annulated 2-quinolones [1080], benzazepines [1081,1082], 1-azaspiro [5.5]undacanes [1083], N-sulfonyl-2-quinolinones [1084], bis(silyl)- [3]-ferrocenophanes [1085], ferroceno-quinolines and -isoquinolines [1086], polycyclic hydrocarbons [1087], cyclic ␣-arylthiophosphonate esters [1088], carbohydrate-based macrolides [1089], fused carbazoles [157], 4-methyl-5-alkyl-2(5H)-furanones [1090], bibicyclo [8.8.8]hexacosanes [1091], bicyclic imidazoles [1092], bicyclic phosphates [1093], bicyclic lactams [1094], hexofuranose-like imino sugars [1095], C8-glycomimeti...…”

A Stereoselective Route to Aza‐C‐aryl Glycosides from Arynes and Chiral Nitrones

“…Contrary to our expectations, treatment with LAH in ether and THF14 under reflux conditions also failed to deliver the required product (Table 3, Entry 3). Attempted reductive cleavage of the N–O bond in the presence of Zn dust under various conditions with different additives was also not helpful either at room temperature,15 or under sonication at 40 °C16 (Table 3, Entries 4, 5 and 6) 17. Eventually, treatment of cycloadduct 12 with Zn dust, acetic acid and water at 70 °C for 2 h18 paved the way for smooth formation of product 38 in 83 % yield (Table 3, Entry 7).…”

Metalated Heterocycles in Organic Synthesis: Recent Applications

“…74 This heteroaryllithium has been also employed in addition reactions to benzyloxyacetaldoximes. 75 In addition, 2-lithiobenzothiazoles have been used recently in addition reactions to a fuconolactone 76 and to an arginine-derived Weinreb amide. 77 If the 2-position in thiazoles is blocked, the lithiation takes place directly at the 5-position, an example being the synthesis of 5-thiazole ketones by reaction of n-butyllithium-generated 5-thiazolyllithiums with nitriles.…”